Adaptive output feedback control of feedforward nonlinear distributed delay systems with unknown delay kernel

<p>This paper considers the problem of global adaptive output feedback regulation for a class of uncertain feedforward nonlinear distributed delay systems. Compared with the existing results, we reduce the conservatism of the restrictive conditions by combining the dynamic scaling technique and the backstepping method, in particular, uncertain control coefficients and unknown delay kernels are admitted. With the help of the Lyapunov–Krasovskii theorem, a delay-independent output feedback controller is proposed by constructing an input-driven observer with a novel dynamic gain, which guarantees that all the closed-loop signals are globally bounded while rendering the states of original system and the estimate states globally asymptotically to converge to zero as time goes to infinity. Finally, a numerical example is given to illustrate the usefulness of our results.</p

Time-varying state-feedback stabilisation of stochastic feedforward nonlinear systems with unknown growth rate

<p>We consider the time-varying state-feedback stabilisation problem for a class of stochastic feedforward nonlinear systems with unknown growth rate in this paper. A new LaSalle-type theorem for stochastic time-varying systems is firstly established by using the generalized weakly positive definite function. As an application, to deal with serious uncertainties in the unknown growth rate, a time-varying approach, rather than an adaptive one, is adopted to design the scheme of a state-feedback controller for stochastic feedforward systems. Based on the established LaSalle-type theorem, it is shown that all signals of the resulting closed-loop system converge to zero almost surely. Illustrative examples are given to verify the theoretical findings.</p

Flow cytometric measurements of wild-type and mutant LDLR internalization activity in transfected HEK-293 cells.

<p>The transfected cells were incubated in serum-free media containing 20 μg/ml Dil-LDL at 37°C for 4 hours. The upper-right area of the dot plots represents EGFP and LDLR double positive cells. (A) Transfected with wild-type; (B) Transfected with the G615V mutant LDLR; (C) Transfected with the C201F mutant LDLR; (D) The histogram shows the percentage of fluorescence for each of the mutations relative to wild-type LDLR. The results are representative of the means ± SD for three independent experiments.</p

The DNA sequencing results of the two FH probands.

<p>(A) The <i>LDLR</i> gene of proband 1. The arrow indicates the G>T missense mutation at position 1907 of the thirteenth exon resulting in a glycine to valine substitution; (B) The <i>LDLR</i> gene of proband 2. The arrow indicates the G>T missense mutation at position 665 of the fourth exon resulting in a cysteine to phenylalanine substitution.</p

Confocal laser images of wild-type, G615V and C201F LDLR activity in transfected HEK-293 cells.

<p>Cells were incubated with 1,1′-dioctadecyl-3,3,3′3′-tetramethylindocarbocyanine perchlorate (Dil)-conjugated LDL for 4 hours at 37°C. Overlays are shown in the right panels with co-localization appearing yellow. Similar results were obtained in 3 separate experiments.</p

Confocal laser images of wild-type, G615V and C201F LDLR localization in transfected HEK-293 cells.

<p>Cells were incubated with tetramethylrhodamine-conjugated concanavalin A at room temperature for 1 hour. Overlays are shown in the right panels with co-localization appearing yellow. Similar results were obtained in 3 separate experiments.</p

Flow cytometric measurements of wild-type and mutatant LDLR expression in transfected HEK-293 cells.

<p>The cells were incubated with phycoerythrin (PE)-conjugated mouse monoclonal anti-human LDLR antibody at room temperature for 30 minutes. The upper right area of the dot plots represents EGFP and LDLR double positive cells. (A) Transfected with wild-type; (B) Transfected with the G615V mutant LDLR; (C) Transfected with the C201F mutant LDLR; (D) The histogram shows the percentage of fluorescence for each of the mutations relative to wild-type. The results are representative of the means ± SD for three independent experiments.</p

Functional Characterization of Two Low-Density Lipoprotein Receptor Gene Mutations in Two Chinese Patients with Familial Hypercholesterolemia

<div><p>Background</p><p>Familial hypercholesterolemia (FH) is an autosomal dominant disease that primarily results from mutations in the low-density lipoprotein receptor (<i>LDLR</i>) gene. We investigated two unrelated Chinese FH patients using gene screening and functional analysis to reveal the pathogenicity and the mechanism by which these mutations cause FH.</p><p>Methods</p><p>First, the <i>LDLR</i> gene was sequenced in these patients. Then, mutant receptors were transfected into human embryo kidney 293(HEK-293) cells, and a confocal laser-scanning microscope was used to observe the localization of mutant proteins. Further, the expression and the internalization activity were analyzed by flow cytometry. Finally, LDLR protein expression and stability was detected by western blot.</p><p>Results</p><p>Two different <i>LDLR</i> class 2B mutations were detected in two patients. The C201F mutation is a known mutation. However, the G615V mutation is novel. Flow cytometry showed that the expression and internalization activity of the mutant LDLRs were reduced to 73.6% and 82.6% for G615V and 33.2% and 33.5% for C201F, respectively.</p><p>Conclusions</p><p>This study identified two <i>LDLR</i> mutations in Chinese patients with FH and analyzed the relationship between the genotype and phenotype of these patients. We found that these mutant LDLRs were defective in transport, which led to a reduction in cholesterol clearance. These results increase our understanding of the mutational spectrum of FH in the Chinese population.</p></div

Clinical features and gene identification results of the probands and their first relatives.

<p>Clinical features and gene identification results of the probands and their first relatives.</p